What the Anesthesiologist Should Know before the Operative Procedure

Endocrine disorders are important causes of perioperative morbidity and mortality. Nearly all are associated with changes in fluid and electrolyte homeostasis and hemodynamic alterations from dysfunction of the hypothalamic pituitary adrenal axis. Because nearly all tissues respond to endocrine hormones, endocrine diseases are associated with multisystem disease. Diabetes mellitus and thyroid disease are relatively common during pregnancy. Most other endocrine disorders are either very rare or are associated with impaired fertility and therefore occur only rarely in parturients. Unfortunately, this leads to the situation in which only a very limited number of case reports have described anesthesia in pregnant women with these diseases. Thus, management is best guided by considering the known systemic effects of the disease processes.

Overview

Diabetes mellitus: This condition is the most common comorbidity in pregnancy, occurring in 1 in 12 pregnant women and in as many as 1 in 7 non-Hispanic blacks.

Implications for the anesthesiologist include long-term macro-or microvascular complications.

Thyroid disease: Subclinical thyroid disease is actually more common in pregnancy than is diabetes.

Up to 15% of pregnant women exhibit hyperthyroidism during their pregnancy with an additional 5% having hypothyroidism. However, more than 90% of the cases of hyperthyroidism are related to gestational transient thyrotoxicosis, which is generally only problematic when associated with hyperemesis gravidarum.

While hyperthyroidism remains a serious disease in pregnancy in the United States (1 in 500 parturients have Grave's disease), most hypothyroidism worldwide results from insufficient iodine in the diet, a condition rare in the United States. In the United States, most hypothyroidism results from chronic lymphocytic (Hashimoto's) thyroiditis.

The critical issues related to thyroid disease revolve around the stresses the hypermetabolic state places on the mother, the risk of thyroid storm, which can be triggered by infection, stroke, diabetic ketoacidosis, surgery and drug therapy, the severe effects of hypothyroidism on fetal development (especially the brain), and the cardiac and neurologic effects of alternations in thyroid function. Euthyroidism should be maintained during pregnancy by control of hyperthyroid conditions and/or supplementation with thyroid hormone as needed.

Other endocrine disorders: These other endocrine disorders, which may be seen in pregnancy, include Addison's disease, diabetes insipidus, hyperaldonsteronism, hypopituitarism (especially postpartum), carcinoid syndrome, Cushing syndrome, pituitary tumors (e.g., prolactinomas), hyperparathyroidism, pheochromocytomas, and multiple endocrine neoplasia. In pregnant women, the chief concerns in these conditions are fluid and electrolyte disturbances and cardiovascular instability. Often endocrine diseases overlap. For example, hypothyroidism may occur in association with Addison's disease. Often treatment of the primary disease is needed to ensure the secondary disease responds to treatment.

Patients with diabetic nephropathy may have fetuses with IUGR (intrauterine growth restriction) and preterm birth. Poor glucose control in the first trimester increases the risk of congenital anomalies.

Fetal glucose disposition

The fetal liver has limited storage of glucose. Excess glucose is converted to fat. Fetuses of diabetic mothers, therefore, have a greater percentage of fat mass. This correlates with obesity and diabetes in later life.

Asymmetric septal hypertrophy

Chronic hyperglycemia is thought to lead to neonatal septal hypertrophy. The enlarged septum can affect the mitral valve leading to subaortic left ventricular outflow tract obstruction. This may mimic hyaline membrane disease. The septal hypertrophy is generally transient.

Effects of human chorionic gonadotropin on thyroid function during pregnancy

Although normal human chorionic gonadotropin (hCG) has mild thyrotropic activity, due to structural similarities with thyroid stimulating hormone (TSH), it is only about 1/10 as potent and thus does not lead to clinical hyperthyroidism.

Variants of hCG have potent thyroid stimulating activity and lead to hyperthyroidism. This is likely the case in gestational trophoblastic diseases including hydatidiform mole and choriocarcinoma (60% will have evidence of hyperthyroidism) and perhaps accounts for up to 2/3 of cases of hyperemesis gravidarum (HG).

Hyperemesis gravidarum occurs in 1.5% of pregnancies, is characterized by severe nausea, vomiting, weight loss, dehydration, and ketosis, and is thought to be related to high hCG levels. The frequent hyperthyroidism seen in HG makes it difficult to distinguish gestational transient thyrotoxicosis (a result of hCG) from Graves' disease. The distinction is all the more difficult because the hyperthyroidism from Graves' disease also may result in hyperemesis. In the usual case of HG, however, the symptoms resolve with both fluid replacement and the normal decrease in hCG that occurs near the end of the first trimester or occasionally within the second trimester.

Fetal effects of thyrotoxicosis

Fetal effects of hypothyroidism

Low maternal circulating thyroxine levels are strongly associated with poor brain development and low IQ. As thyroxine need increases during pregnancy, it is important to assess TSH levels in parturients to ensure adequate thyroid hormone supplementation is given.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

In women with endocrine disorders without maternal or fetal distress, delay in delivery until preoperative information is obtained is mandatory. A blood sugar or electrolyte determination may demonstrate a cause of maternal or fetal distress without causing significant delay. Correction of hypovolemia may improve both maternal and fetus status.

Quite rarely, situations occur in pregnant women, such as severe trauma or a ruptured uterus, where delay in surgery cannot occur. More common, maternal or fetal conditions (e.g, hypertension, altered consciousness, or late fetal heart rate decelerations) seem to dictate urgent delivery. In these cases, it must be recognized that metabolic derangements associated with endocrine disease affect both the mother and fetus.

The prevention and/or treatment of hyper- or hypotension, hyper- or hypoglycemia and electrolyte disorders lead to improved maternal and fetal outcome. In certain situations (e.g., diabetic ketoacidosis [DKA]), rapid delivery of the infant may increase the risk to the mother and the fetus, even in the face of apparent fetal distress. Furthermore, about 1 in 5 cases of DKA occur in patients not previously known to have diabetes.

Most pregnant women with endocrine disease will not present for surgery with untreated severe disease. However, subclinical cases of several endocrine disorders may mimic pregnancy and remain undiagnosed. For example, the many manifestations of hyperthyroidism mimic pregnancy to the degree that some cases of hyperthyroidism may not be diagnosed and women could present with uncontrolled thyrotoxicosis.

Women with uncontrolled endocrine disease usually have multiple system involvement. In hyperthyroid disease, for example, the mother may present with nausea and vomiting, dysrhythmias and palpitations, hyperdynamic circulation, muscle weakness, cardiomegaly, lymphocytic or eosinophillic myocardial infiltrates, heart failure (CHF), and emotional lability. Women with untreated hypothyroidism may present with a cardiomyopathy, fluid retention, slow mentation or altered consciousness.

Emergent surgery issues

Diabetes

In emergent surgery that cannot be delayed due to immediate risks to the mother and/or fetus, the complications of diabetes mellitus can significantly worsen outcome for both the mother and the infant.

A rapid sequence induction and intubation may reveal that the patient has an unexpected difficult airway with stiff joint syndrome and very limited neck extension and mouth opening.

Microvascular and macrovascular complications of diabetes put the patient at significant risk. These include:

Atherosclerotic disease and hypertension that can lead to silent myocardial ischemia (all complications of diabetic dyslipidemia).

Diabetic patients are often obese, adding further potential anesthetic and surgical complications including concerns of sleep apnea, thromboembolic disease, and infection risks, among others.

Emergent surgery puts the diabetic patient at significant risk for the development of diabetic ketoacidosis, severe dehydration, and acute tubular necrosis, especially if the patient has type 1 diabetes mellitus.

In cases with neurologic insults, neurologic outcome is worsened by elevated blood glucose.

Thyroid disease

Emergent surgery in the hyperthyroid patient may lead to excessive thyroid hormone release from the stresses of surgery. The first manifestation would be tachycardia which may be controlled with beta-blockers. However, dysrhythmias and heart failure, or alternatively, thyroid storm may occur.

Release of thyroid hormones is decreased by iodide therapy, and beta-blockers impair the peripheral conversion of T4 to T3. Iodide therapy should be preceded by anti-thyroid drugs by 1–2 hour because iodide alone increases thyroid hormone stores. Important: beta-blocker therapy should be continued postoperatively until the patient has been made euthyroid.

No intravenous anti-thyroid drugs are available and the onset of action of oral anti-thyroid drugs is slow. In contrast, the effect of iodide in inhibiting the release of thyroid hormone is immediate. Cases in which iodide and beta-blocker therapy have been used alone suggest it is an acceptable approach, although the degree of safety is less than when anti-thyroid drugs are also given.

Iodine allergic patients can be given lithium carbonate although lithium is teratogenic in the first trimester and is only used if anti-thyroid drugs cannot be given (e.g., when their administration resulted in agranulocytosis).

Iodide crosses the placenta and causes fetal goiter and hypothyroidism and long-term use is contraindicated in pregnancy.

Other endocrine diseases

Clinical clues to endocrine disease include a number of assessments that may be easily and rapidly performed even in emergencies. These include: evaluation of BP (blood pressure), HR (heart rate), pulse pressure, oxygen saturation; cardiac rhythm and Q-T and P-R intervals on the ECG (electrocardiography); skin turgor, airway, muscle strength, and medication history. The anesthetic technique should be modified based on this rapid screen. In particular, airway abnormalities, severe hypertension, dysrhythmias, and signs of hypovolemia demand extra caution before proceeding with rapid sequence induction.

Urgent surgery issues

With urgent surgery, sufficient time allows a more detailed medical history, measurement of blood glucose and electrolyte levels, and a more thorough evaluation of the patient's physical status, especially the airway, neck flexibility, and cardiopulmonary status. In diabetes, for example, correction of hypoglycemia, volume depletion, electrolyte disorders or blood pressure may correct fetal distress or improve maternal condition to the point that a full evaluation is possible.

Thyroid disease

Evaluations of the airway, cardiopulmonary status (including ECG), and volume status are performed. A CBC (complete blood count) with a differential and a platelet count should reveal the presence of anemia, thrombocytopenia or agranulocytosis, a rare complication of treatment with anti-thyroid drugs (PTU [propylthiouracil], methimazole).

Elective surgery issues

Diabetes

Management of diabetes begins in the preconceptual period. Women with diabetes should strive to achieve a normal BMI (body mass index) and good glycemic control before becoming pregnant. This approach markedly reduces the incidence of congenital anomalies.

After conception, careful and frequent evaluation of glycemic control is critical to avoid both maternal and fetal complications. Changes in insulin requirements occur as pregnancy progresses. With good long-term glycemic control, the anesthesiologist can continue the patient's therapies with only minor modifications for elective surgery.

Many previously nondiabetic patients develop gestational diabetes mellitus, a likely early indicator of high risk for the eventual development of type 2 diabetes. All comorbidities need to be considered and evaluated, including those mentioned above in the discussion of emergent surgery.

Thyroid disease

Patients should be made euthyroid before elective surgery. Nonetheless, being euthyroid does not eliminate risks resulting from the disease and the patient should be properly assessed.

Safe medications during pregnancy

Preconceptual counseling pertaining to medications that are safe for use in pregnancy should occur. Women on ACE inhibitors or ARBs to treat hypertension and delay diabetic nephropathy must find alternative medications as these drugs are fetal teratogens. Most oral hypoglycemic agents are contraindicated during pregnancy with possible exceptions being glyburide, metformin and acarbose.

Thyroid hormones are acceptable during pregnancy but radioactive ablation of the thyroid gland is not. Antithyroid hormones are not uniformly considered acceptable but safe alternatives are not available to replace them.

Growth hormone receptor blockers, octreotide, and bromocriptine have been used safely in pregnancies complicated by acromegaly or pituitary adenomas.

Corticosteroids are safe for use in pregnancy.

Diabetes and the fetus

Women with diabetes who wish to become pregnant should know that the risk of serious birth injury is as much as ten-fold that of a nondiabetic patient of similar body weight, and that the risk for cesarean section is three-fold. Since much of this risk arises from poor glycemic control, the woman must be compliant with strict medical guidelines to promote a better outcome for herself and her offspring.

2. Preoperative evaluation

Diabetes

The primary considerations in pregnant diabetic women are (1) medication management to achieve glycemic control, (2) the effects of diabetes on the mode of delivery, (3) management of associated hypertension and/or preeclampsia, (4) evaluation of other micro- and macrovascular changes resulting from the diabetes, particularly cardiac and renal disease, (5) atlanto-occipital joint immobility, and (6) consideration of the fetal/neonatal effects of the chronic hyperglycemic state.

Medically unstable conditions warranting further evaluation

The endocrine patient is no different from other patients in requiring immediate evaluation of medically unstable conditions. However, the likelihood that an unstable condition stems from the endocrine-related disease should be kept in mind.

Delaying surgery may be indicated

Patients with loss of consciousness, electrolyte disorders, acidosis, blood glucose <60 mg/dL or >160 mg/dL, signs or symptoms of heart disease, elevated creatinine or fetal concerns related to poor diabetic control should have surgery delayed until complete evaluation of those conditions can be used to guide management. Similarly, any patient who is not euthyroid should have surgery delayed until treated. Such delay will reduce the risk of perioperative morbidities by >90%.

3. What are the implications of co-existing disease on perioperative care?

a. Head, ears, eyes, nose, throat

Pregnancy is associated with various degrees of edema, including facial and pharyngeal swelling. These conditions often increase during labor and delivery, making potential laryngoscopy more difficult. Thus, the effect of pregnancy magnifies the risks associated with diabetes or thyroid disease alone.

Diabetes

Diabetic retinopathy is relatively rare in patients of reproductive age but is possible women with long standing type 1 diabetes (>15 years), particularly if glucose control has been poor and the patient has also had hypertension. Tight glucose control and blood pressure management are indicated. Prepregnancy laser photocoagulation has been suggested as a means to limit progression of the retinopathy during pregnancy.

Impaired joint mobility at the atlanto-occipital joint occurs due to glycosylation of collagen. This will be manifested as decreased neck range of motion, painful neck movement, and possibly a positive prayer sign.

Thyroid disease

The ophthalmopathy of thyroid disease presents as upper eye lid retraction and proptosis, a result of infiltration of orbital connective tissue with deposition of collagen and glycosaminoglycans in the muscles. A lid lag and exophthalmos can lead to eye damage and eye moistening and protection is needed during surgery. The patient with significant exophthalmos should be examined preoperatively for visual field defects and loss of color vision. The presence of diabetes increases the risk of ophthalmic pathology in patients in thyroid disease.

Thyroid disease is not strongly associated with joint disorders but muscle weakness and the possibility of a neck mass with tracheal deviation must be considered. Fever and sore throat may result from agranulocytosis after antithyroid drug use and are indications for a CBC with differential.

b. Cardiovascular system

Diabetes

The most frequent unstable cardiovascular condition in the diabetic pregnant woman is likely severe hypertension. Evaluation should include a review of medications and an investigation of its cause, in particular, whether it is a result of preeclampsia or renal disease.

Laboratory studies including creatinine and urinary protein should be considered and a neurologic examination should be performed.

Myocardial ischemia is the leading cause of mortality in the diabetic patient and although acute myocardial infarction is rare in pregnancy, it is associated with a maternal death rate of 20–37%.

More recently, post cardiac transplant patients have increasingly chosen to become pregnant. These patients have an increased incidence of coronary artery disease although no reports have been published of myocardial infarction associated with pregnancy in these patients.

Each of these cardiac conditions may lead to acute heart failure, especially given the hyperdynamic circulation imposed by pregnancy. In evaluating these patients, it is important to obtain a thorough history including exercise tolerance, medications, and prior investigations. As patients with cardiac disease are often placed on activity restriction, their recent exercise tolerance may be uncertain.

Physical examination should focus on signs of acute heart failure such as the presence of an S3, rales or jugular venous distention. Echocardiography should be an early test as it can lead to precise diagnoses and an estimate of cardiac function. In some centers, anesthesiologists are doing screening evaluations using bedside echocardiography with the ultrasound machines they use for regional block. I only recommend this if you have training and expertise in performing such examinations.

Thyroid disease

Patients with hypo- and hyperthyroidism both are at risk for perioperative heart failure.

Hypothyroidism may cause a reversible cardiomyopathy manifested by bradycardia and a low ejection fraction. Septal thickening with idiopathic hypertrophic subaortic stenosis has been described.

Hyperthyroidism usually causes tachycardia, with 90% of patients having HR >90 bpm. Atrial fibrillation is the most common complication and mitral valve prolapse occurs not infrequently. Heart failure in hyperthyroidism is generally high output failure that results from low SVR in the face of tachycardia, myocardial hypertrophy and increased plasma volume.

Other endocrine diseases

Acromegaly may lead to dysrhythmias, hyper-triglyceridemia leading to coronary artery disease, and diastolic dysfunction. However, most reports of pregnant women with acromegaly have not found cardiac disease in the parturients. Numerous electrolyte disorders increase the risk of dysrhythmias and heart failure.

Hyperkalemia, hyponatremia and hypoglycemia may occur with adrenal insufficiency (Addison's disease). Hypotension associated with these electrolyte abnormalities, and which does not respond to pressor agents, should bring adrenal insufficiency to mind. Diagnosis during pregnancy may be difficult and endocrine consultation is recommended.Hyperaldosteronism leads to hypertension and dysrhythmias from hypokalemia and hypomagnesemia. Cushing's syndrome has similar findings including hyperglycemia.

Hyperparathyroidism may be associated with hypercalcemia-related arrhythmias.

Hypomagnesemia may occur with diabetes or with poor nutrition, diarrhea and massive blood transfusion. Hypomagnesemia leads to a wide QRS, decreased contractility, impaired diastolic relaxation and the risk of Torsades de pointes. It is frequently associated with hypocalcemia and hypokalemia and the lack of response to therapy for hypocalcemia and hypokalemia suggest the need for magnesium replacement. Low magnesium, calcium and potassium accompanied by metabolic alkalosis also may be an indication of an inherited disorder of sodium transport in the renal tubule known as Gitelman's syndrome.A similar disorder, Bartter syndrome, also leads to low magnesium and potassium and a metabolic alkalosis. However, hypercalcemia rather than hypocalcemia is more likely occur in this syndrome.

Pheochromocytoma has frequently been described in pregnancy and may present as a component of Sipple syndrome (with medullary carcinoma of the thyroid and parathyroid hyperplasia). Cardiac findings of palpitations, severe hypertension, and marked tachycardia are likely and cases of peripartum cardiomyopathy, catecholamine crisis and CV collapse have been described.

Diabetes

Management goals should be to maintain tight glucose control and avoid cardiovascular instability. The diabetic patient is likely to have both microvascular and macrovascular disease. The former will correlate with the patient's blood sugar control but the latter appear unrelated to blood sugar although they might be influenced by control of the diabetic dyslipidemia and control of hypertension.

ACE inhibitors or angiotensin receptor blockers are generally used along with statins in the non-pregnant diabetic patient to control blood pressure, provide renal disease progression prophylaxis and to treat the dyslipidemia. However, each of these drugs is contraindicated in pregnancy.

Best management of the hypertension and dyslipidemia includes weight loss, blood sugar control, exercise, cessation of smoking and a low-sodium diet. Aggressive therapy of hypertension is also indicated to help prevent diabetic nephropathy although no specific drug acceptable in pregnancy has been shown to improve long-term outcome. Nonetheless, as hypertension during pregnancy is associated with adverse outcomes, treatment is indicated.

Thyroid disease

In thyroid disease, the goal should be to normalize heart rate, using thyroid-replacement in hypothyroidism and beta-blockade and antithyroid drugs in hyperthyroidism.

The hypothyroid patient (with either overt or subclinical disease) is at risk for the development of coronary artery disease (CAD), in part because dyslipidemia is a prominent feature of hypothyroidism. The risk of hypothyroid-related CAD is much higher in women than men. Hypothyroidism also is associated with increased rates of diabetes, thus magnifying the risk. Thyroxine therapy of the hypothyroid patient is thought to decrease insulin resistance and improve the dyslipidemia although a beneficial effect of such therapy on CAD is less clear.

Torsades de pointes

This lethal dysrhythmia is significantly more common in women than men, thus making it more likely in pregnancy. The clinician should be aware that methadone, even at low dose, is associated with a prolonged QT interval and sudden death from Torsades de Pointes. Methadone therapy is increasingly being used for chronic pain as an alternative to "more dangerous" opioids. Antidepressants may further increase the QT interval.

c. Pulmonary

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is rare in parturients.

Diabetes

Diabetes leads to an increased risk for pulmonary infections that will exacerbate COPD. In addition to routine examination of the chest, preoperative evaluation of the patient with COPD would include an evaluation of the baseline blood gases and possible pulmonary function tests.

The primary risk reduction strategy would be cessation of smoking and avoidance of allergens. Early treatment of sinus infections and/or allergic rhinitis may minimize exacerbations. Oral decongestants have been associated with gastroschisis and should be avoided. Newer antihistamines have been used without known fetal effects. Should the number of recent exacerbations be high, preoperative respiratory therapy may be indicated.

Placement of an arterial line for arterial blood gases (ABGs) would be helpful. Awareness of the possibility of pneumothorax reminds the anesthesiologist to minimize plateau pressure during controlled ventilation.

Other endocrine diseases

Muscle weakness with respiratory insufficiency is a feature of many endocrine diseases including Addison's disease, Cushing's syndrome and many electrolyte abnormalities. Hypophosphatemia is a cause of proximal muscle weakness. Hyperthyroidism
and especially hypothyroidism may be associated with muscle weakness and impaired weaning from mechanical ventilation. A markedly elevated creatine kinase level may be found in hypothyroid myopathy.Hypomagnesemia (diabetes, diarrhea), hypocalcemia (hypoparathyroidism, etc.) and histamine-like substances in carcinoid syndrome may lead to bronchospasm and laryngospasm. Obstructive sleep apnea is strongly associated with acromegaly.

Reactive airway disease (asthma)

Asthma in the pregnant woman may improve, deteriorate or stay the same during pregnancy. She should be assessed for dyspnea, cough, nocturnal dyspnea, as well as the effects of chronic medications (e.g., steroids) on her blood sugar control (HbA1c). PFTs should be reviewed in severe cases for the reversibility of bronchoconstriction with bronchodilators. Auscultation of the chest may reveal wheezing and a decreased I:E ratio. As noted above, both hypomagnesemia and hypocalcemia may increase bronchospasm.

FEV1 can be roughly estimated by having the patient exhale forcefully. However, studies have shown that physicians poorly estimate FEV1 in this manner and use of a spirometric device provides a more objective indication of asthma severity.

Diabetes

Asthma medications may complicate the control of blood sugar and a pregnant woman's response to those blood sugars. Excessive insulin dosing in response to blood sugar spikes may lead to recurrent hypoglycemia. Both beta agonists and corticosteroids increase blood sugar and if needed, are preferably used in their inhaled forms rather than orally to minimize effects of blood glucose. ß-agonists are also associated with hypokalemia whereas steroids may lead to adrenal insufficiency necessitating perioperative steroid supplementation. Refractory hypotension may occur in patients without such supplementation.

Cromolyn and leukotriene receptor antagonists (e.g., montelukast and zafirlukast) appear to be safe in pregnancy although sufficient data on the latter are lacking. As in COPD, the primary risk reduction strategy is the cessation of smoking and avoidance of allergens.

Pulmonary embolism

Suspicion of a pulmonary embolism (tachycardia, tachypnea, pleuritic chest pain) can be confirmed with echocardiography. A significant embolism leads to a dilated, hypokinetic right atrium and ventricle.

A spiral computed tomograpy (CT) or (less effective) ventiltation/perfusion lung (V/Q) scan can be used to rule out a pulmonary embolism as it has a low incidence of false negative findings in pregnant women.

d. Renal-GI

Diabetes

Proteinuria is the first sign of progressive renal disease and usually precedes increases in BUN and creatinine. Perioperative evaluation of the diabetic patient with renal disease should start by looking at the patient's renal history during pregnancy. Has she had any urinary tract infections (UTIs) or acute pyelonephritis? Glucosuria is a risk for a UTI.

Hyperemesis gravidarum is a risk factor for acute renal failure in early pregnancy as are septic abortion (and other causes of sepsis) and ovarian hyperstimulation syndrome. Hyperemesis gravidarum leads to dehydration and the potential for prerenal disease. Unlike the non-pregnant patient in which a prerenal insult is more likely to lead to transient acute tubular necrosis, during pregnancy the same insult may lead to cortical necrosis and permanent renal impairment. Thus dehydration and causes of acute tubular necrosis should be promptly corrected.

Patients with diabetes are more likely to have preeclampsia, another risk for acute renal failure, especially when the preeclampsia is superimposed on preexisting hypertension.

The greatest risk for acute renal failure follows massive hemorrhage. Thus, the best prevention is avoidance of significant hemorrhage or adequate replacement therapy should hemorrhage occur. This requires a coordinated effort between the obstetrician, anesthesiologist, laboratory, blood bank and nursing staff.

Significant abdominal pain with vomiting, polyuria and dyspnea should prompt evaluation for diabetic ketoacidosis (DKA). Ketone bodies on a urinary multistick, fruity breath, tachycardia and normothermia or even hypothermia would be usual. DKA particularly occurs with type 1 diabetes and is much less common with type 2.

Diabetic patients with chronic renal insufficiency should be evaluated for anemia and platelet dysfunction, autonomic dysfunction and peripheral neuropathy. Laboratory studies should include serum chemistries including Blood urea nitrogen (BUN) and creatinine and electrolytes including potassium.

Thyroid disease

Hyperthyroidism is usually associated with increased renal blood flow and GFR and a decreased renal vascular resistance. The patient is expected to have a slight decrease in creatinine. Thus an elevated creatinine level should lead the investigator to look to other causes, e.g., hyperemesis gravidarum. Hyperthyroidism per se may result in polyuria and dehydration but usually does not lead to renal pathology. In contrast, hypothyroidism can lead to severe myopathy that can lead to renal failure (primarily as result of rhabdomyolysis) although this is quite rare. Renal disease may also result from heart failure related to hyper- or hypothyroidism.

Other endocrine diseases

Virtually all endocrine diseases have renal effects. Some directly alter the concentrations of hormones that have renal actions (i.e., aldosterone and vasopressin) thereby producing electrolyte disorders. Others affect cardiac output and renal preload or afterload (e.g., carcinoid syndrome, pheochromocytoma). Hyperparathyroidism is associated with GERD and renal stones, with up to half of patients presenting with renal calculi.

Hyperemesis gravidarum

Both diabetes and thyroid disease increase the risk of hyperemesis gravidarum and patients with persistent nausea and vomiting should be checked for these disorders.

Hyperemesis gravidarum also is associated with gestational trophoblastic disease, hydrops fetalis and fetal karyotypic abnormalities. For patients presenting with recent hyperemesis gravidarum, the clinician needs to consider the impact of vomiting on electrolyte balance. If total parenteral nutrition was used, the risk of catheter infection should be strongly considered as a cause of any sepsis.

e. Neurologic:

Thyroid disease

The hyperthyroid patient is likely to have emotional lability and anxiety and will benefit from sedation before surgery. In contrast, the hypothyroid patient may be depressed, lethargic or even obtunded.

Acute issues

Diabetes

Acute neurologic changes that are not focal are an indication for immediate evaluation of blood glucose, electrolytes and medication history, both illicit and accidental. Insulin overdose can be accidental or intentional, but in either case may be fatal. The level of glucose (high or low) leading to symptoms varies widely among patients.

Further evaluation should look to signs of cerebral edema or hemorrhage including edema of the optic disks, anisocoria, deviations of gaze, etc. Amaurosis fugax should lead to evaluation of the vascular system for plaque or a deep vein thrombosis (DVT). 25% of patients will have a patent foramen ovale through which a clot can pass to the cerebral circulation. Isolated visual changes may be related to vitreal hemorrhages or detached retinas from diabeti retinopathy.

Hypoglycemia, DKA, the hyperosmotic hyperosmolar syndrome, and hyponatremia can lead to confusion or coma.

Seizures, intracerebral bleeds, ruptured aneurysms and subarachnoid hemorrhages are other causes of altered consciousness that can be seen in pregnancy. Patients suspected of these disorders should have a review of their history for hypertension, prior epilepsy, preeclampsia, head trauma, etc. Neuro-imaging (e.g., CT and magnetic resonance imaging [MRI]) is generally indicated to confirm the diagnosis.

Other endocrine disorders

A postpartum patient who presents with headache, meningeal signs, bitemporal hemianopsia, cerebral edema, hypotension and electrolyte abnormalities may have postpartum pituitary necrosis (Sheehan's syndrome). Supportive care should be initiated with diagnosis confirmed by CT or MRI.

Severe hypernatremia with dehydration and hyperosmolarity may suggest the presence of diabetes insipidus which can occur after Sheehan's syndrome, head trauma or other pituitary lesions. Intracranial causes of diabetes insipidus are treated with DDAVP (desmopressin).

An obtunded patient with hypothermia, bradycardia, hyporeflexia, edema, ascites and/or pleural effusions should have evaluation for hypothyroidism while neurologic imaging studies are obtained to rule out CNS disease. Confirmation should lead to immediate administration of liothyronine (T3) as well as IV hydrocortisone in case of hypothyroid-induced secondary adrenal insufficiency.

An insulinoma is suggested by low basal blood glucose and elevated insulin and C-peptide levels. Patients with insulinomas may be found comatose or seizing, but often rapidly respond to the administration of glucose. Most cases present in the first trimester although cases throughout pregnancy have been reported. Glucagon has been used during pregnancy to maintain glucose levels although in some women, symptoms improve as insulin resistance occurs with increasing gestational age. Surgery involves ultrasound examination of the pancreas to locate the tumors, which are generally benign.

Chronic disease

Diabetes

The primary chronic neurologic concerns in diabetic patients include diabetic autonomic neuropathy (DAN) and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is rare in pregnancy because it usually develops only after longstanding disease. However, women with lifelong type 1 DM may be seen with neuropathy.

Thyroid disease

Hypothyroidism is a risk factor for neurologic changes including depression, bipolar disease, impaired mentation, and lethargy. It should be considered in any patient with mental slowness, decreased deep tendon reflexes, bradycardia, weight gain, and edema.

Other endocrine disorders

Diabetic autonomic neuropathy (DAN)

Patient with DAN present with a resting tachycardia and decreased heart rate variation with respirations. There may be impaired gastric secretion and motility. Of significant concern is the potential loss of warning signs of hypoglycemia (catecholamine release with diaphoresis and tremulousness). Autonomic neuropathy may lead to impaired gastric secretion and motility, thus increasing the risk of full stomach and aspiration.

Diabetic peripheral neuropathy

The peripheral neuropathy of diabetes is marked by a diffuse sensory polyneuropathy often with a stocking glove distribution. Large fiber disease leads to a loss of light touch, proprioception, and muscle strength. Small fiber disease leads to a change in pain and temperature sensation with dysesthesias, paresthesias, and neuropathic pain. Any neuropathy should be documented so subsequent regional anesthesia is not implicated as causative.

Sheehan syndrome

Gestational enlargement of the pituitary combined with peripartum hypotension may lead to ischemia and necrosis of the pituitary. Later, antibodies to pituitary tissue may attack the remaining gland to cause gland involution and loss of pituitary function. The syndrome may present in a variety of ways depending on which hormones are deficient. (PMID 20944496) A concern can be the initiation of thyroid replacement hormone therapy before assessment of the pituitary-adrenocortical axis because this may precipitate an adrenal crisis. Pituitary hypofunctioning should be considered in the differential of postpartum depression.

f. Endocrine:

Acute issues

Hyperglycemia from lack of insulin activity (insulin resistance) leads to dehydration, tissue hypoglycemia with release of ketone bodies, electrolyte depletion and multiorgan dysfunction. The fetus may be unable to secrete adequate insulin and may also have DKA.

Initial treatment focuses on the reestablishment of intravascular volume, correction of acidosis, and normalization of glucose and electrolytes. Thus preoperative evaluation should include evaluation of blood glucose, sodium, potassium and ABGs.

The incidence of thyroid storm is about 1% of hyperthyroid pregnant women. It is associated with a high incidence of heart failure.

Pheochromocytoma: A tumor of the catecholamine-producing cells of the adrenal medulla although the tumor may arise in many tissues. Stress that releases catecholamines can release marked levels of these substances with resulting extreme hypertension and the on-going threat of intracerebral hematomas and stroke. Long-standing disease leads to dehydration with and polycythemia, cardiac dysfunction, decreases in insulin secretion, and hyperglycemia. Palpation of the abdomen may trigger a catecholamine crisis.

Chronic issues

Acromegaly increases insulin resistance and the risk of gestational diabetes and hypertension.

Cushing's syndrome is strongly associated with hypertension and diabetes. About 10% of reported cases in pregnancy are complicated by preeclampsia, with an unusually high incidence of pulmonary edema also reported. Poor wound healing is likely. Fetal effects include premature labor (usual), IUGR and perinatal death. However, because of high placental metabolism of maternal cortisol, neonatal adrenal insufficiency is rare.

Treatment of diabetic ketoacidosis

Normal saline in initiated to rehydrate the patient and restore hemodynamic stability. Up to 2.5 L may be needed. This rehydration is generally associated with a 30% to 50% decrease in the blood glucose (BS) level.

Crystalloid (0.5 NS) with regular insulin (0.1 U/kg/h) is then initiated until BS decreases to <250 mg/dL (usually 4–6 hours). The average decline in blood glucose is 75 to 100 mg/dL. Insulin is continued until pH is >7.3, HCO3 is >18 mEq/L and BS is normal.

Sodium bicarbonate is only indicated if the pH is <6.9, the patient has severe hyperkalemia, or if the patient is not responding to vasopressors and the pH is <7.1.

Caution must be taken to avoid cerebral edema which is more likely if the BS is corrected without simultaneous correction of serum sodium levels. Additional electrolytes including K2PO4 and Mg may be needed as correction occurs. Electrolytes and BS should be checked hourly.

Treatment of thyroid storm

Thyroid storm is associated with a hypermetabolic state and, therefore, the first steps in treating include IV fluids and cooling measures as in malignant hyperthermia (MH).

Initial therapy is aimed at inhibition of thyroid peroxidase (TPO), the enzyme that catalyzes the addition of iodide to thyroglobulin. This is done with PTU (800 mg po STAT, then 200–400 mg q 8 h via NG tube).

Beta-blockers are given to lower the HR to 90 bpm. Beta-blockers (e.g., propranolol 1–2 mg q 5 min up to 6 mg, or preferably an esmolol drip) also block the conversion of T4 to T3.

Plasmaphoresis or single pass albumin dialysis may be effective adjuvants, especially in patients with contraindications to antithyroid drugs (PMID 20439250; PMID 20420590).

Treatment of pheochromocytoma

Selective alpha-1 blockade (phenoxybenzamine, doxazosin, phentolamine) and aggressive volume expansion are the mainstays of treatment. Adequate alpha blockade is indicated by minimal residual orthostatic hypotension, maximum blood pressures of 160/90 mmHg and an absence of significant dysrhythmias. Persistent tachycardia is an indication to add a ß-blocker but should only be done after an alpha blockade is clearly established to avoid severe vasoconstriction. Metyrosine (FDA Pregnancy category C) has been used to inhibit catecholamine synthesis in cases of malignant pheochromocytoma. Magnesium sulfate has also been used to improve cardiovascular stability and has been recommended by some authors as standard therapy.

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

Musculoskeletal system

Nonenzymatic glycosylation of proteins and cross-linking of collagen in diabetes
decreases the range of motion of joints, especially cervical motion and the temporomandibular joint.

Autoimmune thyroid disease may mimic rheumatoid arthritis with findings of myopathy andarthropathy. Cases of thyrotoxic periodic paralysis in pregnancy have been described. As in nonthyroid associated periodic paralysis, hypokalemia and impaired glucose tolerance are prominent features.

Acromegaly is associated with carpal tunnel syndrome, myopathy and osteoporosis. Hyperparathyroidism may also lead to osteoporosis, osteopenia and bone pain.

Cushing disease is associated with osteoporosis that may lead to vertebral compression fractures.

Integumentary system

Thyrotoxicosis leads to hair loss, pretibial myxedema, onycholysis and acropachy. Hypothyroidism also leads to hair loss as well as myxedematous changes in the hands and periorbital region.

Nonpitting edema of the posterior neck and upper back (diabetic scleroderma) in diabetes may make neck extension more difficult. Other cutaneous manifestations of diabetes include acanthosis nigricans
and necrobiosis lipoidica diabeticorum.

The presence of neurofibromatosis type 1 and paroxysmal hypertension suggests the presence of a pheochromocytoma.

Hypopituitarism is associated with thin skin, fine wrinkling and a yellowish pallor to the skin.

4. What are the patient's medications and how should they be managed in the perioperative period?

N/A

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

Diabetes

The anesthesiologist should be well acquainted with the various forms of insulin and oral hypoglycemic agents. During pregnancy, insulin requirements initially decrease in the first trimester and then increase in the second trimester (perhaps more related to the degree of obesity than the degree of increased blood glucose). At term, the insulin requirement in type 1 DM typically is 20% to 30% higher than when nonpregnant. With type 2, insulin resistance can cause the needed dose to be as much as 150% of the nonpregnant dose.

Oral hypoglycemic agents, which may have been used when nonpregnant, are generally contraindicated in pregnancy, with most patients therefore using insulin for control of blood glucose levels.

The short acting insulins including human regular insulin (Humulin, Humulin R), and the rapid-acting insulin analogs (aspart [Novalog] and lispro [Humalog]) have been shown to be safe in pregnancy. Human insulin combined with protamine creates an intermediate-acting insulin (NPH [Humulin N or Novolin NPH]) that can provide activity through the nighttime hours. Long-acting insulin analogs, with the exception of glargine (Lantus) have not been determined to be safe in pregnancy. The extended action of Lantus may make nocturnal hypoglycemia a problem during pregnancy because of the greater demands for glucose of the pregnant woman. Thus, short-acting or rapid-acting insulins plus NPH are preferred during pregnancy. (See below.)

A novel therapy in phase 3 trials for the treatment of type 2 diabetes is the use of a highly selective inhibitor of the renal sodium-glucose cotransporter-2 (dapagliflozin and others). This therapy significantly lowers blood glucose using an insulin-independent mechanism of action (increased urinary excretion resulting from decreased glucose reuptake in the proximal tubule). Further, in trials, hypoglycemia from the drug has been a rare event and its use has been associated with weight loss and possibly reduced hypertension. Benefits or harms to the kidney and other organs are not yet known.

Thyroid disease

Compliance with thyroid hormone replacement, including the increased dose requirement in pregnancy, is important to avoid complications of hypothyroidism. Usual dose is 0.1 to 0.2 mg / day. Patients treated for hyperthyroidism should be monitored for the possible development of hypothyroidism after treatment. Inadequate treatment of hypothyroidism may impair adrenal function and thus hydrocortisone 100 mg q 8 hours should be considered. Myxedema coma is best treated with T3 (0.15–0.3 µg/kg q 6 h) as well as corticosteroid coverage.

In patients with hyperthyroidism, the minimum dose of anti-thyroid drug should be used that can maintain free T4 at the upper limit of normal and TSH at the lower level of normal. Although PTU is preferred in the U.S., it has similar toxicities to methimazole, including agranulocytosis. Beta-blockers should be used to control symptoms of hyperthyroidism (palpitations, shaking, anxiety, tachycardia).

Other endocrine diseases

Acromegaly: Octreotide, a somatostatin analogue given IM monthly, is occasionally continued during pregnancy. Neither octreotide nor lanreotide has been associated with adverse effects during pregnancy but they do cross the placenta and thus their routine use in pregnancy is not recommended. A newer therapy is the growth hormone receptor blocker pegvisomant (FDA pregnancy category B). Acromegaly has also been treated with dopamine agonists, such as bromocriptine, a drug more often used in the treatment of prolactinomas. Bromocriptine use is considered safe and effective though it is usually discontinued with pregnancy and reintroduced only if signs of tumor enlargement occur (headache, visual field changes, diabetes insipidus).

Cushing syndrome during pregnancy has been treated with metyrapone and ketoconazole although most authorities suggest surgical treatment in the first or second trimester is preferred.

Corticosteroids doses should be increased to cover the stress of surgery. Labor and delivery involve similar stress and parenteral stress-dose coverage should be used.

Diabetes insipidus: Deamino-D-arginine vasopressin (DDAVP) is used to treat central DI and transient DI of pregnancy. Thiazide diuretics are used in nephrogenic DI. The usual doses are continued.

i. What should be recommended with regard to continuation of medications taken chronically?

Diabetes

All type 1 and severe type 2 diabetics need insulin treatment perioperatively (even those usually maintained on oral hypoglycemic drugs). In addition, any diabetic undergoing major surgery needs insulin as the stress response will otherwise lead to hyperglycemia.

In severe disease, preoperative euglycemia should be established with an insulin drip initiated 2 hours before surgery. Intraoperative glucose levels should be maintained between 120 mg/dL and 180 mg/dL. Important (and notable since postoperative glucose control has been an SCIP measure), sliding glucose scales using short-acting SQ insulin DO NOT provide adequate glucose control to avoid episodes of hyperglycemia as they are reactive rather than proactive in management.

Labor management

Neonatal hypoglycemia and perinatal asphyxia correlate with maternal hyperglycemia during labor, so attempts should be made to maintain maternal euglycemia during labor. For type 1 DM or severe type 2 DM, a combined insulin and glucose infusion is usually preferred. D5W is begun at 100 mL/h and regular insulin at 0.5 unit/h. Hourly BS is measured and the infusion rate adjusted according to the result. Large increases in BS are additionally treated with boluses of 2­-5 units of regular insulin.

Alternatively, half of the normal AM insulin dose may be given and regular insulin administered as determined by laboratory values. In this scenario, usual bolus doses range from 2 to 5 units. For mild type 2 DM and diet-controlled GDM, simply withholding all dextrose from IV fluids is often sufficient to achieve normoglycemia.

Cesarean section

Patients having CS should be scheduled early in the morning and receive their usual dose of NPH or glyburide the night before. A D5W infusion should be started with IV boluses given on a sliding scale to maintain maternal glucose at 80 to 160 mg/dL.

Thyroid disease

Patients with hyperthyroidism should continue anti-thyroid drugs until they are euthyroid.

Hypothyroid patients should continue their thyroxine. Patients with Grave's disease as the etiology of their hypothyroidism are more likely to require increased dosing as pregnancy progresses. Dosage requirements may increase by 30% as early as the fifth week of gestation, with additional increases as pregnancy continues.

Other endocrine diseases

Adrenaline sufficiency: chronic treatment with cortisone or hydrocortisone provides adequate mineralocorticoid activity as long as the patient is receiving 125 mg daily (cortisone) or 100 mg daily (hydrocortisone). Fludrocortisone 0.1 mg/day may be used when corticosteroid doses are further decreased. In stress situations including surgery, the normal adrenal gland output of cortisol rises to 250 to 300 mg/day and this dose should be used in the perioperative period (e.g., hydrocortisone 100 mg q8h). Methylprednisolone, triamcinolone, betamethasone, and dexamethasone have no mineralocorticoid activity and are not sufficient substitutes in adrenal insufficiency.

Cardiac

ACE inhibitors, ARBs, and statins will have been discontinued before pregnancy because of the risks of fetal harm. Other antihypertensive agents (e.g., oral methyldopa) should be continued in their usual doses as control of hypertension is important in minimizing the complications of diabetes. Beta-blockers are associated with neonatal hypoglycemia and may exacerbate maternal hypoglycemic episodes as they inhibit lipolysis.

Preeclamptic patients: Intravenous (IV) magnesium sulfate is the drug of choice in patients with severe preeclampsia or eclampsia as its cerebrovasodilator effects reverse cerebral vasospasm. For acute control of hypertension, labetalol has advantages over hydralazine in that it does not lead to reflex tachycardia or ICP.

Pulmonary

Beta-agonists and corticosteroids increase blood glucose and may affect insulin requirements. All immunosuppressant drugs used in post-transplant patients should be continued, although some adjustments may be made in pregnant women. For example, mycophenolate mofetil has been associated with increased adverse fetal outcomes. Of note, lung transplant recipients are at the highest risk for poor pregnancy outcomes.

Renal

ACE inhibitors and ARBs used for renal protection should be discontinued before pregnancy because of the risks of fetal harm. Renal transplant patients should continue antihypertensives (beta-blockers, alpha methyldopa, hydralazine or calcium channel blockers with the goal of maintaining BP at no greater than 130/80 mm Hg. All immunosuppressive medications are Food and Drug Administration (FDA) category B or higher but successful outcome of pregnancy in renal transplant patients requires ongoing immunosuppression to avoid graft rejection. Concerns of fetal loss and malformations are higher with mycophenolic-acid containing drugs. Acute rejection nonetheless is greater in pregnant women than nonpregnant.

Neurologic

Women with multiple sclerosis may be treated with interferon and become pregnant during such therapy. Other uses for interferon include treatment of chronic viral hepatitis and certain neoplasms. Interferon may cause hypo- or hyperthyroidism, particular in patients with Grave's disease. Interferon is usually discontinued upon planning for or discovering a pregnancy because the teratogenicity of immunomodulation is uncertain.

Anticoagulants

Pregnancy increases the risk of thromboembolism. Patients with additional risks (e.g., history of prior pregnancy loss or deep vein thromboses) often are given anticoagulant therapy. Diabetic parturients are often obese and at increased risk for thromboembolism. As thromboprophylaxis, many may receive low molecular-weight heparin during pregnancy, more so if they also have thrombophilias (e.g., factor V Leiden or antiphospholipid syndrome).These drugs should be discontinued to allow regional anesthesia (if planned) and restarted postoperatively. The specific time intervals should follow the American Society of Regional Anesthesia (ASRA) guidelines. Of interest, evidence supporting the role of thrombophilias in adverse pregnancy outcome is lacking (PMID21262448 and others).

Psychiatric

Schizophrenia affects 1% to 2% of the population with a peak in the reproductive ages. In general, the risks from stopping antipsychotic drugs (inability to care for themselves or their infants, suicide, infanticide, etc.) are thought to outweigh any benefits. Thus, these drugs should be continued in their usual doses. No definite associations have been found between the use of antipsychotics during pregnancy and adverse pregnancy outcomes. Special care should be taken in diabetic patients since some antipsychotic drugs (the "atypical or second-generation" antipsychotics clozapine and olanzapine) are known to increase the occurrence of hyperglycemia and hyperlipidemia. Changing from an atypical antipsychotic to another antipsychotic has been associated with hypoglycemic episodes.

j. How To modify care for patients with known allergies -

Patients allergic to NPH insulin may combine a long-acting insulin with short-acting insulins. Glargine is thought to be a safe long-acting insulin in pregnancy but it is associated with a higher risk of nocturnal hypoglycemia than NPH insulin.

Patients needing antithyroid therapy who are allergic to iodine may be given lithium carbonate 300 mg PO q 6 hours. Though lithium has been linked to teratogenicity, the association is uncertain. Rarely, lithium has been reported to act as thyroid stimulant.

l. Does the patient have any antibiotic allergies- - Common antibiotic allergies and alternative antibiotics]

N/A

m. Does the patient have a history of allergy to anesthesia?

Malignant hyperthermia

Documented:

Avoid all trigger agents such as succinylcholine and inhalational agents. Follow a proposed general anesthetic plan: total intravenous anesthesia with propofol ± opioid infusion ± nitrous oxide. Ensure that an MH cart is available [MH protocol].

MH is rare during pregnancy and other diagnoses should be considered with MH is suspected, although MH may result when triggering agents are given in an MH-susceptible patient. No cases of MH have been reported with labor and delivery in the absence of triggering agents.

Among other conditions to be considered, thyroid storm is suggested by a history of tremors, fatigue, or dyspnea. Palpation of the thyroid may reveal an enlarged gland. Malignant neuroleptic syndrome (MNS) should also be considered, particularly in women taking anti-psychotic drugs. MNS typically presents with fever, autonomic instability, leukocytosis, tremor, muscle rigidity, encephalopathy, and an elevated CPK. Serotonin syndrome (the possible cause of death of Libby Zion) presents with myoclonus, hyperthermia, tachycardia, hypertension, and mental alterations. Severe cases generally involve the administration of both a monoamine oxidase inhibitor (e.g., phenelzine) and serotonin agonists.

5. What laboratory tests should be obtained and has everything been reviewed?

Hemoglobin levels

In general, no acute changes in hemoglobin will be related to endocrine disease. Target hemoglobin levels should be based on the need for oxygen delivery, especially as related to the cardiovascular system. In the absence of direct measures of oxygen extraction, hemoglobin levels should be maintained above 8 g/dL in women with coronary artery disease.

Polycythemia may be seen in pheochromocytoma and adrenal adenomas with Cushing's syndrome. Although nonspecific, an elevated hemoglobin level also may be indicative of dehydration.

Anemia: Both hypothyroidism and hypopituitarism lead to a normochromic-normocyticanemia. Microcytosis should lead to consideration of coexisting iron deficiency. Often in endocrine disease (e.g., hypothyroidism, Addison disease), plasma volume is decreased so that the anemia is masked by hemoconcentration.

Electrolytes

Most endocrine diseases are associated with electrolyte disturbances. The particular pattern of electrolyte disturbance may help identify the etiology. For example, unexplained hypokalemia may lead to the diagnosis of Cushing's syndrome or hyperaldosteronism.

Hypomagnesemic state: endocrine causes

Diabetic ketoacidosis

Hyperaldosteronism

Primary hyperparathyroidism

Bartter syndrome

SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Coagulation panel

Hypothyroidism is associated with an acquired von Willebrand syndrome (type 1) with increased risk of bleeding. The syndrome responds to thyroid hormone replacement. In contrast, hyperthyroidism may lead to a hypercoagulable state with increased thromboses. Most other endocrine disorders and, in particular, hypercortisolism, have been associated with alterations in coagulation and an increased risk of thrombotic events. Thromboprophylaxis has been suggested for patients with Cushing's syndrome.

Imaging

Magnetic resonance imaging is used during pregnancy to examine the pituitary for adenomas and the adrenal gland for pheochromocytomas and adrenal adenomas. Ultrasound may also be used for imaging adrenal tumors. Combined with the fine needle aspiration biopsy, ultrasound is the primary means of surveying the thyroid gland during pregnancy.

Diabetes

The key laboratory test in the diabetic patient is the blood glucose. A hemoglobin A1c level may indicate the degree of recent glycemic control. Normal range in pregnancy is 4.1–5.9%. RBC hemoglobin is nonenzymatically glycosylated by glucose that freely crosses the RBC membrane. The percent glycosylated is proportional to the average glucose concentration over the preceding 60–90 days. The urine should be examined for ketones and proteinuria. Serum electrolytes are helpful in a variety of conditions as discussed above.

Diagnosis of gestational diabetes mellitus

A 100-g oral glucose tolerance test should be performed in a fasting parturient. GDM is indicated by any two of the following: Fasting glucose ≥ 95 mg/dL; 1-hour ≥ 180 mg/dL; 2-hour ≥ 155 mg/dL; 3-hour ≥ 140 mg/dL.

Thyroid disease

TSH levels are normally slightly depressed in the first trimester due to high HCG levels. TSH levels in the first trimester above 2.5 mIU/L are associated with early pregnancy loss and preterm delivery. Thyroxine replacement is indicated when mildly elevated TSH (>2.5 mIU/L) occurs in the presence of thyroid antibodies. Low TSH levels are an indication to perform a free T4 and free T3 test. The goal of thyroid treatment in pregnancy is to avoid both hyperthyroidism and low T4 levels.

Other endocrine diseases

Increased 24-hour urine fractionated metanephrines and serum chromogranin-A levels are diagnostic of pheochromocytoma, although many cases are found incidentally on abdominal CT or MRI.

In the first trimester, maternal T4 is the source of fetal thyroid hormone and low supply of T4 is associated with poor fetal developmental outcome. As maternal T3 may be present in sufficient quantities to suppress TSH (especially in low-iodine environments), both free T4 and TSH levels should be measured to ensure adequate T4 is available to the fetus.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

A general statement about the various options should be covered here. Specifics regarding the appropriateness (for the general option) and the benefits/drawbacks/issues (e.g., antiplatelet agents for regional) should be included in each section. In the regional section, include any adjuvants like common sedation or general. A discussion of patient positioning and any special concerns with regard to positioning injury should be included.

Pregnancies in women with endocrine disease, with the exception of diabetes mellitus and thyroid disease, are rare with few case reports detailing management, particularly as related to labor and delivery. Most recommendations related to choice of anesthetic technique in endocrine disease are based, therefore, on management of the disease in the nonpregnant patient, with considerations of the physiologic changes in pregnancy and the maternal/fetal effects of pharmacologic interventions.

In many, if not most cases, regional anesthesia is less invasive than general anesthesia and is performed with drugs that have an extensive safety record in pregnancy. On the other hand, general anesthesia may provide a more stable hemodynamic environment when rapid induction of anesthesia is needed, is associated with complete amnesia, and can be used in patients with contraindications to regional anesthesia.

Most often, the choice of anesthetic technique is far less important than the proper perioperative management of the disease. Emphasis should, therefore, be placed more on management of the pathologic features of the disease than the choice of anesthetic per se. That being said, some conditions (e.g., difficult airway or bleeding diathesis) may lead the practitioner to choose a particular preferred anesthetic technique.

Neuraxial

Benefits

Diabetes: Neuraxial anesthesia in the diabetic patient has the obvious advantage of the ability to monitor the patient's level of consciousness and thus, indirectly, hypoglycemic events. The greatest benefit of neuraxial anesthesia in the pregnant diabetic women is the ability to adapt the anesthetic to the changes in the obstetric plan that may occur during labor. For example, shoulder dystocia is more likely and may lead to urgent cesarean section. The presence of an epidural catheter would allow a rapid increase in the block density to allow for surgery. Diabetes is associated with a significant number of adverse obstetric outcomes including a four-fold increase in preeclampsia, a three-fold increase in induction of labor and a 2.5-fold increase in cesarean section. Epidural analgesia is advantageous in each of these situations. It is particularly advantageous in decreasing the need for general anesthesia in this population.

Thyroid disease: In the euthyroid patient, the choice of RA versus GA should be based on the surgical needs. Avoidance of airway manipulation may be useful in hyperthyroidism or in situations where the thyroid gland has compromised the airway through destruction, a mass effect, or changes in vascularity. The slow onset of epidural block that may be produced might be useful in patients with cardiomyopathy from hypothyroidism. RA allows the continuous assessment of mentation in the hypothyroid patient and may avoid problems with postoperative weakness requiring ventilatory support after GA. However, respiratory compromise has been described postoperatively after spinal anesthesia in a parturient with an enlarged thyroid gland.

Other endocrine diseases: Most case reports of anesthesia in parturients with endocrine disease appear to involve the use of regional anesthesia. When combined procedures are performed, such as cesarean section followed by tumor removal, neuraxial analgesia is often used for delivery of the fetus with general anesthesia then induced for the surgical procedure. Reported advantages are that the mother can be awake and aware of the delivery of her child but then have satisfactory anesthesia, including hemodynamic stability, during the removal of her endocrine tumor (e.g., a pheochromocytoma). Several cases of pregnant women with pheochromocytomas have been reported in which delivery (vaginal or CS) was accomplished using epidural analgesia and the tumor removal was performed using general anesthesia.

Drawbacks

Diabetes: Diabetes is commonly associated with obesity, which may complicate the surgical procedure. An inadequate block may lead to the need to induce general anesthesia urgently or emergently, with greater risk than elective induction.

The clearance of lidocaine and its metabolite is decreased in diabetic women, increasing the possibility of local anesthetic-induced toxicity.

Peripheral neuropathies should be documented before regional anesthesia. Volume status should be considered before performing neuraxial block. Patients with co-existing renal disease may have platelet dysfunction as may patients with preeclampsia and HELLP syndrome.

Other endocrine diseases:Cushing's disease and acromegaly
may be associated with musculoskeletal changes that make regional block more difficult (e.g., osteoporosis with vertebral collapse). The cardiovascular instability associated with pheochromocytoma seems to mandate the use of general anesthesia during tumor resection although the successful use of regional anesthesia has been described.

Issues

Diabetes: Diabetic patients are more likely to be obese and as a result it may be more difficult to perform neuraxial anesthesia. However, the availability of ultrasound technology is lessening this challenge. Even with regional anesthesia, rapid changes in insulin requirement and blood glucose levels may occur.

Thyroid disease: The attainment of preoperative euthyroidism is important to minimize morbidity. The infant should have his or her thyroid status determined with early treatment of hypothyroidism indicated. Infants of hyperthyroid mothers may develop neonatal Grave's disease from transplacental transfer of thyroid stimulating immunoglobulin. These infants may require transient therapy to control the symptoms of hyperthyroidism.

Peripheral nerve block

Benefits

Peripheral nerve blocks trespass less on the mother and fetus in terms of hemodynamic effects than would neuraxial or general anesthesia. Though hematomas are a concern in patients with coagulopathies, they are likely less consequential and easier to both diagnose and control than neuraxial bleeds. With skill, peripheral nerve blocks can provide anesthesia for many surgical procedures. They will not be adequate for vaginal or cesarean delivery, however.

Drawbacks

Not all patients tolerate surgery under peripheral nerve block. This is particularly true of long surgeries, procedures using tourniquets, needle-phobic patients, and those having anxiety. Although anxiolysis and analgesia can be administered to improve tolerance, the therapeutic margin of sedation in pregnancy is slim. Loss of airway, aspiration, fetal depression, and even maternal cardiovascular depression are all readily produced by relatively small sedative doses administered during pregnancy. Further, the risk of intravascular toxicity is increased in the pregnant woman because of higher cardiac output. Sedation may mask or abolish the patient's ability to recognize or report signs of local anesthetic toxicity.

Identification of local anesthetic toxicity

Note that the signs are extremely variable and not all may occur in a given case.

Vasopressin is avoided, as are calcium channel blockers and beta blockers

Amiodarone for ventricular arrhythmias (rather than lidocaine or procainamide)

Increase lipid emulsion to 0.5 mL/kg/min.

Initiate cardiopulmonary bypass if arrest situation is still present.

Use prolonged monitoring after cardiac toxicity has occurred due to risk of recurrence.

Diabetes: Peripheral neuropathies should be documented before regional anesthesia. Impaired nerve conduction in diabetic patients results in increased sensitivity to block and to injury. Local anesthetic toxicity must be avoided and lower concentrations of local anesthetic may be used. The use of epinephrine to decrease toxicity may have adverse fetal effects and may increase the risk of injury to the nerve. Further, the use of stimulation may be less successful in identifying a nerve, possibly increasing the risk of intraneuronal injections. Thus, great care is required in performing these blocks during pregnancy. Elective surgery is best delayed until the postpartum period.

Issues

Diabetes: Peripheral blocks will be increasingly used in diabetic pregnant women as they reduce respiratory and cardiac stresses and can manage painful conditions associated with the disease. The risks of greater nerve damage are likely real but the incidence of such damage is rare, making peripheral nerve blocks acceptable for use in these patients.

General anesthesia

Diabetes: Options for anesthesia in the diabetic parturient are based on the surgical procedure and co-existing diseases. During general anesthesia, attention to the possibilities of gastroparesis (an indication for IV metoclopramide), hemodynamic instability from autonomic dysfunction, and airway difficulties from atlanto-occipital joint immobility must be considered. Furthermore, patients with poor glucose control are likely to have had an osmotic diuresis and may be hypovolemic or have electrolyte disorders. The greater difficulty of intubation in both pregnant and obese women combined with the effects of diabetes serve to discourage the routine use of general anesthesia in this population. Induction and intubation should be managed to avoid hypertension and cardiac stress as well as hypotension from hypovolemia and autonomic dysfunction. Frequent blood glucose determinations should be made (at least q 1 hour).

Thyroid disease: Euthyroid patients are not at increased risk related to the choice of anesthesia.

Benefits

As in other patients, general anesthesia has the advantage that it can be rapidly induced while providing complete comfort to the patient. Invasive testing can proceed without patient concern of pain associated with the procedures. Wide swings in hemodynamic function are better tolerated during general anesthesia than neuraxial anesthesia because the anesthetized patient does not exhibit nausea, vomiting, or alternations in mentation that could lead to patient distress, patient movement and further instability. Invasive monitoring, especially TEE, is more acceptable during general anesthesia.

Drawbacks

Diabetes: The diabetic patient has significant risks for general anesthesia related to her disease. These include difficult airway, possible gastroparesis, and hemodynamic instability. In addition, the diabetic patient has decreased responsiveness to hypercarbia, which may lead to respiratory difficulties during awakening.

Thyroid disease: Untreated and undertreated hypothyroidism is likely to be associated with hypothermia, hyponatremia, hypotension, hypoglycemia, and potential hear failure. GA is best avoided as postoperative cognitive function may be difficult to assess and respiratory insufficiency may occur due to generalized weakness. In hyperthyroid patients, general anesthesia may relax the pharynx and increase the difficulty of intubation when the trachea has been compressed. Awake intubation should be considered. Inadequately treated patients will be at increased risk for thyroid storm.

Other endocrine diseases:Cushing's disease may be associated with hypertension, decreased respiratory muscle mass, and obesity. These may make GA more difficult. In addition, gastric ulcerations may increase the risk of GI bleed. Pulmonary edema is more likely in these patients.

Other issues

Diabetic ketoacidosis should lead to delay in surgery to avoid a moribund outcome (exceptions might be cases in which the DKA is caused by an abscess). Aggressive rehydration, insulin, and correction of electrolytes are paramount.

Airway concerns

Aside from the usual airway concerns in pregnancy, e.g., facial and pharyngeal edema and airway friability, the diabetic patient may have a diabetic sclerodema of the upper back and neck, atlanto-occipital joint stiffness, and obesity, all which combine to create a more difficult airway. A careful examination of the airway early in labor and repeated examination just before a surgery are indicated. Body positioning to assure the best alignment of the airway axes is important. The Cushing patient may have limited neck movement from the buffalo hump and increased fat deposition in the neck and sternal areas.

Monitored anesthesia care (MAC)

Benefits

MAC can allow minor procedures to be done safely with little cardiovascular, pulmonary or renal trespass. In patients with endocrine diseases, however, careful attention must be paid to airway changes (e.g., thyroid masses, hyperglossia, friable mucus membranes, etc.) since airway loss is more likely with even mild sedation.

Drawbacks

MAC is not without risks. Patients with moderate sedation may startle and disrupt the surgical procedure. Oversedation and airway obstruction are more likely in patients with endocrine disorders.

6. What is the author's preferred method of anesthesia technique and why?

What prophylactic antibiotics should be administered?

Preoperative antibiotics should be considered in diabetic patients with infectious complications such as urinary tract infections or recurrent bronchitis. Patients receiving preoperative antibiotics may have sufficient coverage that additional prophylactic antibiotics are not needed, assuming the preoperative antibiotics have a spectrum that meets the recommended prophylactic antibiotic for the surgery in question. Patients with adrenal insufficiency are particularly prone to infectious complications and appropriate prophylaxis is indicated.

What do I need to know about the surgical technique to optimize my anesthetic care?

Optimization of anesthesia care requires knowledge of the surgical procedure including patient positioning, duration of procedure, risks for nausea and vomiting, and degree of postoperative pain expected. Prone position procedures may require increased eye protection in a diabetic patient with retinopathy. Skin precautions should be taken, particularly in diabetic patients and those with Cushing's syndrome. Postoperative pain may lead to silent myocardial ischemia in patients at risk unless adequately controlled.

Labor and delivery

In general, neuraxial analgesia will be chosen for labor and delivery in pregnant women with endocrine disease, with the choice of spinal versus epidural dependent on the woman's cardiac status, urgency of procedure, practitioner experience and the preferences of the patient, anesthesiologist, and surgeon. IV PCA with fentanyl or remifentanil is an acceptable alternative in women with contraindications to neuraxial block.

Surgery during pregnancy

Many endocrine diseases are associated with poor pregnancy outcome that is sometimes avoided by removal of the offending gland early in pregnancy. In general, surgery is best performed during the second trimester at which time the risk of preterm labor and fetal anomalies is lowest. In cases where gland manipulation may lead to hemodynamic instability or hormone release (thyroidectomy, adrenalectomy), general anesthesia will be preferred. General anesthesia has the added advantage of producing profound uterine relaxation at a time uterine contractions are unwanted. Fetal monitoring is controversial but may provide information that can lead to alterations in anesthetic management even if delivery is not an option. Thus, from the mid-second trimester, unless the surgical site precludes monitoring, intermittent or continuous external fetal monitoring is often performed.

What can I do intraoperatively to assist the surgeon and optimize patient care?

The use of neuromuscular blockers to facilitate surgery needs to consider the neuromuscular effects of the particular disease. However, in general, normal doses of NMBs may be used. Intraoperative measurement of blood sugar is necessary and should be done at least hourly in patients with diabetes. Tight blood glucose control is associated with better patient outcome as long as hypoglycemic episodes are avoided. Patient positioning should consider the possibility of peripheral neuropathies. Limbs should be padded and protected. Consideration of the patient's renal status and fluid management is imperative to avoid postoperative acute renal failure.

Complications: cardiac

Cardiac complications in patients with endocrine disease include the full spectrum of cardiac disease, from myocardial ischemia to cardiomyopathy. The most concerning is probably silent myocardial ischemia in the diabetic patient. Many endocrine diseases affect the heart, and CHF or hemodynamic instability is a frequent complication, particularly if the vascular fluid status is abnormal as a result of the endocrine dysfunction. Electrolyte disorders may also give rise to various cardiac dysrhythmias. Tachysystoles (e.g., atrial fibrillation) are more common in endocrine diseases.

Complications: pulmonary

Postoperative respiratory insufficiency is more likely in Addison's disease, Cushing's disease, and hypothyroidism. Obstructive sleep apnea is likely in obese patients and those with acromegaly. Specific screening should be applied preoperatively to allow for appropriate placement of the patient postoperatively in a unit with added observation capabilities. Narcotic dosing for postoperative analgesia should be reduced in patients with sleep apnea.

a. Neurologic:

Unique to procedure

Alterations in the postoperative mental state may be particularly difficult to diagnose in the endocrine patient, particularly if baseline mental status was questionable. In addition to residual effects of drugs (e.g., narcotics, muscle relaxants, inhaled agents, etc.), attention should be paid to glucose and electrolyte levels (particularly sodium). Undiagnosed hypothyroidism has been a cause of delayed awakening. Of further concern, hyperglycemia that may result from surgical stress and/or exogenous glucose may worsen any neurologic injury that has occurred.

b. If the patient is intubated, are there any special criteria for extubation?

Prior to extubation, emptying of the stomach with an NG tube should be performed because of the likelihood of gastroparesis. The jaw and neck should be handled with care during mask ventilation to avoid joint disruption. The autonomic neuropathy of diabetes is thought to decrease respiratory drive to hypercapnea so postoperative monitoring of CO2 may be indicated. In addition, diabetic patients, whether they are obese or not, have a significant incidence of obstructive sleep apnea. Muscle weakness from the various endocrine disorders may lead to postoperative respiratory failure and should be assessed preoperatively. The usual extubation criteria apply.

c. Postoperative Management

What analgesic modalities can I implement?

Diabetes per se will not affect the analgesic modality chosen. However, the greater incidence of obstructive sleep apnea and the decreased sensitivity to hypercapnea suggest that increased monitoring for respiratory depression is appropriate. A particularly useful modality is a PCA pump with end-tidal carbon dioxide monitoring tied to a "smart" pump. These pumps have the ability to stop the narcotic infusion should CO2 rise. Pain management should be sufficient to avoid exacerbations of cardiovascular disease (silent myocardial ischemia). Patients with endocrine disease may have alterations in the pharmacokinetics and pharmacodynamics of drugs, and these changes need to be considered. Patients who received neuraxial anesthesia or a peripheral nerve block may have these continued for postoperative pain management. Cesarean delivery patients will often receive neuraxial morphine.

What level bed acuity is appropriate?

After delivery, most endocrine patients can be managed in a step-down unit capable of monitoring for respiratory depression. Patients with neurosurgery or surgery near their airway, e.g., thyroidectomy, usually should be admitted to an ICU. Similarly, patients with other associated severe disease, such as CHF, may require ICU (intensive care unit) admission. Postpartum patients should be able to go to a postpartum bed on Labour and Delivery.

What are common postoperative complications, and ways to prevent and treat them?

The stress of surgery may make postoperative insulin requirements unpredictable. A sliding scale is frequently used to adjust insulin dosage to the BS determination. The insulin requirement in type 1 DM usually decreases 30% to 50% in the immediate postpartum period. In type 1, the decrease may be even more dramatic but is less predictable; thus continued intensive monitoring is required. In general, the glucose-insulin infusion is continued until normal diet is restored. When the mother is breastfeeding insulin requirements will be still lower.

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